It is known to study the metabolism or material exchange of fatty acids in the heart muscle of human and animal subjects in vivo .alpha.-halogenated fatty acids labeled with .sup.34m Cl, .sup.77 Br and .sup.123 I, and with .omega.-.sup.77 Br- or .omega.-.sup.123 I-labeled fatty acids (see Ma-CHULLA et al, Preparation, Quality Control and Stability of .sup.11 C, .sup.34m Cl .sup.77 Br and .sup.123 I labeled Fatty Acids for Heart Muscle Metabolism Studies, Proc. XIV, International Annual Meeting of the Society of Nuclear Medicine, Berlin, 15-18 September 1976.).
The results of such efforts have led to a clinical use of the 17-.sup.123 I -heptadecanoic acid for the in vivo diagnosis of myocardial material exchange (see FREUNDLIEB et al, Use of 17-.sup.123 I-labeled Heptadecanoic Acid for Noninvasively Measuring Myocardic Metabolism, Proc. XV International Annual Meeting of the Society of Nuclear Medicine, Groningen, 3-16 September 1977).
The analogous .sup.18 F-labeled acids were probably not considered applicable for such myocardial studies, because of their presumed high toxicity, especially with even numbers of carbon atoms. Also, the pickup of the labeled acid by the heart muscle was found to increase from member to member along the series .omega.-chloro, .omega.-bromo- and .omega.-iodo-labeled acids with the best pickup being found with the latter.
Surprisingly, we have found that the maximum pickup of certain .omega.-F-fatty acids is greater than that of .omega.-iodo-fatty acids: with .omega.-.sup.18 F-heptadecanoic acid a rapid pickup of a maximum of about 40%/g heart is found with heart muscle.
This advantageous maximum pickup, whose magnitude is comparable to that of 1-.sup.11 C-labeled fatty acids, is accompanied by a delayed elimination as is desired for radiographic studies so that these .omega.-.sup.18 F-labeled fatty acids are especially advantageous for myocardial investigations.
The toxicity usually associated with fluorinated compounds can be countered effectively by the use of these compounds in carrier-free preparations.
The .omega.-.sup.18 F-fatty acids are especially advantageous for radiographic studies in part because the .sup.18 F is a positron emitter with rapid incorporation in conjunction with delayed release, not attainable with various hitherto known preparations.
Because of the advantages of positron-emitting .sup.18 F(T2/3=110 minutes), its use in positron-emission tomography has increased in interest as has the interest in fatty acids labeled therewith. By comparison with .sup.11 C (T2/3=20 minutes) which is also a positron emitter, .sup.18 F has a much longer half life which can increase the circulation path of .sup.18 F labeled radiopharmaceuticals by several hundred km.
ROBINSSON: Biologically Active .sup.18 F-Fluoroorganic Compounds, Proc.Symp.New Devel.Radiopharm.labeled comp., Copenhagen, Bd.I IAEA, Vienna, p.423 (1973), describes .sup.18 F substituted fatty acids of a chain length up to 14 carbon atom having the .sup.18 F substituents in the 2 or .alpha. position. Typical of these compounds are the 2-.sup.18 F-fluorohexanoic acid and 2-.sup.18 F-tetradecanoic acids which have been proposed for myocardial investigations.
.alpha.-.sup.18 F labeled fatty acid esters and their production are described in KARIM et al: Fluorine-18 labeling of Lower Fatty Acids by Heterogeneous Exchange on Gas Chromatographic Columns, J. Lab. Comp. Radiopharm., 13, 519 (1977).
Heart-muscle tests have shown, as to maximum enrichment in the myocardium, that the .alpha..sup.18 Flouro fatty acids are less effective than the corresponding Cl, Br or I compounds, and far less in the combination of surprising effects described above than the corresponding .omega.-.sup.18 F fatty acids.
Another object of the invention is to provide an improved method of investigating heart muscle exchange of radioactive labeled fatty acids.